Restless Legs Syndrome
Conditions
Brief summary
Restless Legs Syndrome (RLS) is a common neurological disorder. Augmentation is the main complication during long-term DA treatment of RLS. This study aims to examine effect of Horizant (Gabapentin Enacarbil) on Augmentation in RLS patients.
Detailed description
This is an Open label single arm study. The purpose of the study is to demonstrate the efficacy of Horizant in patients with RLS who exhibit augmentation while on Dopaminergic therapy. Adult patients (age 18-85 years) with diagnosis of primary RLS (diagnosed by study investigators) with augmentation on dopaminergic therapy will be screened for participation in the study. RLS diagnosis will be made by the study investigators using International RLS study group criteria. Patients with augmentation on dopaminergic therapy as defined by NIH 2007 with ASRS of 5 to 15 will be offered to participate in the study. Inclusion and exclusion criteria are listed below. The study will be performed after approval of the Institutional Review Board of the University of Missouri. A total of 50 subjects will be entered into the study over a period of 1 year. Written consent will be obtained from all patients. After pre-participation evaluation for eligibility, subjects will be selected and enrolled in the study and followed for a total of 6 follow up visits (Days 0, 30, 90, 120, 180, 360). Subjects Enrollment period will last up to 12 months. The total duration of study will be 24 months.
Interventions
DRUGHorizant
Phase1: During phase 1 therapy, Horizant will be added on as an adjunct to all subjects taking part in the study along with stable dose of their current dopaminergic (DA) agent and both medication will be continued for a total period of 90 days from day 0 to day 90. Subjects will be evaluated for three visits (days 0, 30 and 90) during Phase I. Phase 2: At the 90th day follow-up visit, with initiation of phase 2 therapy, all subjects will be tapered off (by 50% reduction in dose each week) of their current dopaminergic agents while maintaining the same dose of Horizant and will be on Horizant monotherapy. All subjects will be evaluated for additional three clinic visits (days 120, 180, 360).
Sponsors
University of Missouri-Columbia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Adult patients with diagnosis of RLS for more than one year. 2. Patients who are on DA therapy for 6 months or longer. 3. Patients who developed Augmentation (on stable dose of DA) lasting for 3 months or longer. 4. Augmentation severity rating scale of 5 to 15. 5. Both males and females 6. Age range = 18-85 year
Exclusion criteria
* Known Hypersensitivity to Horizant or Gabapentin products * Peripheral neuropathy * Radiculopathy * Peripheral vascular disease * Uremia \[abnormal blood urea nitrogen (BUN) or Creatinine on Comprehensive Metabolic Panel (CMP)\] * Anemia * Patients who are currently pregnant * Patients who currently take opioids, lithium, anti-nausea medications (e.g. metoclopramide), dopaminergic antagonists (e.g. Haloperidol), 1st generation antihistamines (e.g. diphenhydramine, pseudoephedrine), anti-psychotic medications and iron therapy. * Subjects with impaired decision making capability.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Augmentation Severity From Day 0 to Day 90 | From Day 0 (Baseline) to Day 90 | Augmentation severity rating scale; 0-24, 0 is better, 24 is worst |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Augmentation Severity Rating Scale Form Day 0 to Day 360 (270 Days After Discontinuation pf Dopaminergic Medication) | Day 0 to day 360 (270 days after discontinuing dopaminergic medication) | Numeric Scale to assess degree of augmentation; Range 0-24; 0 is better, 24 is worst. We compared the Augmentation severity scale on day 0 to day 360 (which is 270 days after this decrease of dopaminergic medication) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label open-label single arm study
Horizant, 600 mg oral once daily at 5 pm for 360 days.
Horizant: Phase1: During phase 1 therapy, Horizant will be added on as an adjunct to all subjects taking part in the study along with stable dose of their current dopaminergic (DA) agent and both medication will be continued for a total period of 90 days from day 0 to day 90. Subjects will be evaluated for three visits (days 0, 30 and 90) during Phase I.
Phase 2: At the 90th day follow-up visit, with initiation of phase 2 therapy, all subjects will be tapered off (by 50% reduction in dose each week) of their current dopaminergic agents while maintaining the same dose of Horizant and will be on Horizant monotherapy. All subjects will be evaluated for additional three clinic visits (days 120, 180, 360). | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Open-label |
|---|---|
| Age, Continuous | 54 years |
| Augmentation Severity rating scale | 7.5 units on a scale |
| IRLS score | 22.5 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 6 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Augmentation Severity From Day 0 to Day 90
Augmentation severity rating scale; 0-24, 0 is better, 24 is worst
Time frame: From Day 0 (Baseline) to Day 90
Population: 10 patients enrolled - 2 dropped out - 8 completed the study
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Open-label | Change in Augmentation Severity From Day 0 to Day 90 | Baseline | 6.5 score on a scale |
| Open-label | Change in Augmentation Severity From Day 0 to Day 90 | 90 days | 0 score on a scale |
p-value: 0.0131Wilcoxon (Mann-Whitney)
Secondary
Change in Augmentation Severity Rating Scale Form Day 0 to Day 360 (270 Days After Discontinuation pf Dopaminergic Medication)
Numeric Scale to assess degree of augmentation; Range 0-24; 0 is better, 24 is worst. We compared the Augmentation severity scale on day 0 to day 360 (which is 270 days after this decrease of dopaminergic medication)
Time frame: Day 0 to day 360 (270 days after discontinuing dopaminergic medication)
Population: Only 8 subjects completed the study to its final point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Open-label | Change in Augmentation Severity Rating Scale Form Day 0 to Day 360 (270 Days After Discontinuation pf Dopaminergic Medication) | Day 0 augmentation scale score | 6.5 score on a scale |
| Open-label | Change in Augmentation Severity Rating Scale Form Day 0 to Day 360 (270 Days After Discontinuation pf Dopaminergic Medication) | Day 360 Augmentation scale score | 0 score on a scale |
p-value: 0.0131Wilcoxon (Mann-Whitney)